A physiologist from Belarus who's worked at the Medical University of South Carolina for almost 10 years thinks she's found a mechanism that could explain why.
"Pulmonary fibrosis is a deadly, very complex disease where the lung's air sacs are replaced by tough fibrotic tissue," Galina Bogatkevich said. Using modern physiological technology called proteomics, Bogatkevich's laboratory compared healthy and diseased lung fluid and found that a key growth factor that is supposed to inhibit fibrotic growth is malfunctioning.
"This is the first time we've identified a physiological difference that parallels the profound differences between black and whites in the severity of the disease and prognosis," she said in an American Physiological Society session at Experimental Biology in San Francisco.
*Paper presentation: "Antifibrotic effect of hepatocyte growth factor is impaired in lung fibroblasts isolated from African-Americans," APS Physiology Airway Mechanics and Mechanotransduction in the Lung 767.9/board #C684. Research was by Galina Stephanie Bogatkevich, Anna Ludwicka-Bradley, D. Beth Singleton and Richard M. Silver, Department of Medicine, Medical University of South Carolina, Charleston.
Proteomic approach finds lowered antifibrotic HGF among black patients
Pulmonary fibrosis (PF) strikes nine of out 10 patients with systemic sclerosis or scleroderma, a group of diseases involving abnormal growth of the connective tissue that supports the skin and internal organs. Current thinking is that pulmonary fibrosis is caused by micro injury to the lung as part of the earlier diseases' progress.
"But we also know that PF is a 'proteomic disease' – that is its pathogenesis depends on the imbalance in expression and communication between many proteins," Bogatkevich noted. Using the proteomic approach they found that the amount of antifibrotic glycoprotein hypatocyte growth factor (HGF) was reduced in the blood and epithelial lining fluid of African-American scleroderma patients than in Caucasians.
And the latest study presented in San Francisco "demonstrates that antifibrotic effects of HGF are impaired in lung fibroblasts isolated from Africa-Americans may be due to the deficiency in c-Met receptor function," Bogatkevich said. "This may explain, in part, the greater severity and worse prognosis for African-American scleroderma patients."
Until now the only therapy for this very difficult group of diseases was palliative: oxygen to increase the chance of breathing success and/or trying to generally boost the immune system. Neither approach is real therapy,
However, "now that we've identified the c-Met malfunction, it gives us a good direction to follow," Bogatkevich said. "It's a promising target that seems to take the same clear track as the disease's population."
First step is "we need to find or develop a suitable animal model where PF can be imposed. Also we plan to do polymorphism studies because probably there are some Whites that have differences in the c-Met function due to damage or signaling difficulties and the results could give us some useful clues."
She said it's also possible "now that we know what to study, that further work on scleroderma itself will be more productive. It's a little simpler disease, and since PF develops from these diseases in the first place, going upstream in the pathogenesis could yield even more useful results. These future studies on the c-Met receptor functionality definitely will advance out understanding of this range of diseases," Bogatkevich concluded.
Funding: Scleroderma Foundation, National Institutes of Health.
Editor's Note: For further information or to schedule an interview with a member of the research team, please contact Mayer Resnick at the APS newsroom @ 415.905.1024 (March 31-April 5); or 301.332.4402 (cell) or 301.634.7209 (office), email@example.com; or Christine Guilfoy at 978.290.2400 (cell) or 301.634.7253 (office).
The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.
APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In May 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).
A searchable online program for EB is at http://www.faseb.org/meetings/eb2006/call/default.htm
Experimental Biology is an annual scientific meeting convened by the Federation of American Societies of Experimental Biology, including the American Physiological Society (APS) and other biomedical societies. The meeting features "nominated" lectures, symposia, research presentations, awards, a job placement center, and an exhibit of scientific equipment, supplies, and publications. This year's participating Societies are APS, American Association of Anatomists, American Society for Biochemistry and Molecular Biology, American Society for Investigative Pathology, American Society for Nutritional Sciences, and the American Society for Pharmacology and Experimental Therapeutics.
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